Human beings must immunologically respond to a wide variety of infectious agents throughout their lifetimes, which span decades. These immune responses require the involvement of T lymphocytes, but nothing is known about how T lymphocyte populations evolve during decades-long exposures to infectious agents.
The research of Peter J. Wettstein, Ph.D., focuses on the analysis of T lymphocyte responses in mice to multiple antigenic challenges with the objective of understanding how T lymphocyte populations evolve in terms of their specificity and diversity. These studies will provide new data that will be important for the development of vaccines and understanding the effects of aging.
- Quantitation of the diversity of T lymphocytes that respond to minor histocompatibility antigens in mouse models and identification of characteristics of T cell receptors that are required for recognition of these antigens.
- Evaluation of the level of competition between memory and naive T lymphocytes in responses to multiple challenges with minor histocompatibility antigens. Dr. Wettstein will test the hypothesis that responses to multiple challenges evolve over time with competition between memory and naive T lymphocytes in order to sustain these responses.
- Examination of the effect of aging on diversity of T lymphocytes that can respond to single antigens and how aging impacts the ability of naive populations to successfully compete with memory T lymphocytes in responses to repeated antigenic challenges.
- Quantitation of the effects of repeated acute infections that require strong T lymphocyte responses on the ability of mice to respond to new challenges with less immunogenic antigens that are similar to tumor-associated antigens. These experiments will test the hypothesis that T lymphocyte responses to acute infections reduce the capacity to respond to new antigenic challenges, such as those provided by vaccinations.
Significance to patient care
Despite the need to respond throughout life to both chronic and acute infections, the body loses its ability to generate new T lymphocytes that may be very important for maintaining lifelong immune responses as well as responding to new challenges with multiple vaccinations for cancer and infectious agents, such as influenza.
The results from Dr. Wettstein's research will tell us how T lymphocyte responses to repeated infections maintain their diversity over time and specifically how new T lymphocytes contribute to those responses while still having the capacity to respond to new antigens. It is anticipated that these studies will point toward the necessity to increase T lymphocyte diversity before vaccinating elderly individuals for infectious diseases and cancer.